Dynamic regulation of rna modifications by AlkB family dioxygenases

We investigated the activity of FeII/alpha-ketoglutarate (alpha-KG)-dependent AlkB family dioxygenase on RNA modifications. RNA modifications have been thought to be an intact part of mature RNA; however, more and more evidences begin to show that these modifications are very dynamic, and can be regulated by stimuli. We found that AlkB domain of AlkBH8 catalyzes hydroxylation of a hypermodified mcm5U in wobble uridine (U34) in tRNA Gly(UCC). This hyper-modification in wobble uridine may regulate translation process. We then discovered that FTO catalyzes the demethylation of m6A in mRNA through the formation of N 6-hydroxymethyladenosine (hm6A) and N 6-formyladenosine (f6A). These relative stable modifications can prevent re-methylation in situ, and may regulate RNA-protein interactions. They could further serve as a label for nascent RNAs. The regulation of RNA modifications can be part of cellular regulatory network and may possess important functions, which potentially provides rapid responses to various cellular and environmental signals, including energy and nutrient availability in mammals.